Effect of mirex on the activities of various rat hepatic mixed-function oxidases.

Abstract

Mirex (dodecachlorooctahydro-1,3,4-metheno-2H-cyclobuta[cd]pentalene) was orally administered to male and female rats at daily dosages of 5, 10, 25, and 50 mg/kg for 5 days and its effects on aniline hydroxylas,p-nitroanisoleO-demethylase, ethyl morphine-N-demethylase, and UDP-glucruonyltransferase activities in the liver were studied. Liver-to-body weight ratios show significant increases at all of the doses tested, reaching maximum of 206 and 230 per cent of controls at a dose of 25 mg/kg for males and females, respectively. Metabolism of each of the substrates is altered by each dose of mirex fed. Aniline hydroxylase activity is decreased at all levels tested and the reduction is progressive with the dose. The Mirex content of rat liver microsomes is, by analysis, 9.69, 14.75, and 36.73 µg per 0.2gram-equivalents of liver microsomes from male rats treated at 10, 25, and 50 mg/kg, respectively. Aniline hydroxylase activity is not affected by addition of up to 400 µg of mirex to the reaction mixtures, using liver preparations from untreated animals.p-Nitroanisole demethylation activity is induced to a maximum in animals treated at 5 mg/kg. Ethyl morphine demethylase is induced to a maximum by 10 mg/kg in male and 25 mg/kg in female rats. Higher doses manifest a reversal ofp-nitroanisole-and ethyl morphine demethylase activities in both the sexes. Although the UDP-glucuronyl transferase specific activity is unaffected by mirex pretreatment, total activity in the liver increases to a maximum of 173 and 149 percent of controls at 25 mg/kg in males and females, respectively. Thus, it appears that chronic low doses of mirex seriously alter hepatic mixed-function oxidase systems of exposed animals, although mirex is not a substrate for any of these enzymes.